8/13/2019 NCUR Poster Final

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OPTIMIZATION OF THE SYNTHESIS OF N-ALKYLBIS 3-ACETAMIDOPROPYL)-N-ALKYLAMMONIUM HALIDES

Donovon Adpressa, Daniel Olson, Chris Evans, and Travis T. Denton*Department of Chemistry and Biochemistry, Eastern Washington University, Cheney, WA

One of the primary focuses of the materials chemistry program at EWU is the synthesis of a series of novel quaternary antimicrobial agents. N -alkylbis(3-acetamidopropyl) N -alkylammonium halides capitalize on electrostatic attractive forces between their own cationic center and the negatively charged

membrane of bacteria to insert a lipophilic tail into the cell membrane, disrupting the pH balance ultimately resulting in the cells death. These quaternarybiocides have proven to be extremely effective antimicrobial agents. The optimization, synthesis and antimicrobial assay results will be discussed.

The initial synthetic strategy used Raney nickel as thecatalytic agent. This approach presented a work up whichyielded excessive amounts of nickel hydroxide waste anda challenging isolation of the compound. Substitution of10% wt. Pd/C as the catalyst resulted in not only a cleanerfaster work up, but faster reaction times.

Acknowledgements:

EWU Department of Chemistry and BiochemistryEWU Alumni AssociationEWU FoundationLeslie Swannack

Scheme 2: Alkylation to yield N -alkylbis(3-acetamidopropyl) N -alkylammonium halides

Scheme 1: Catalytic hydrogenation of N -alkylbis(cyanoethyl)amines to form N -alkylbis(3-

acetamidopropyl)amines

Spectral Characterization

Results:

Further Questions? Email: Donovon.adpressa@eagles.ewu.edu

Choosing an atypical solvent system for the S N2 alkylation

of the product from scheme one yielded a reaction whichprecipitated out of solution as the reaction progressedwhich proved especially helpful in the work up of theseextremely hydroscopic molecules.

n= R= Counter Ion Yield

15 Propargyl Bromide 89%15 Methyl Iodide 83%15 Benzyl Chloride 71%

n= Catalyst Yield ReactionTime

13 Raney Nickel 64%(after recrystallization)

>72hrs

13 Palladium onCarbon

71%(recrystallization unnecessary)

~18hrs

The NMR spectra of N- octadecyl(3-acetamidopropyl)amine[CE-II-107] compared to N- octadecyl(3-acetamidopropyl)propargyl ammonium bromide [DA-I-055]. Peaks at 4.1 and 2.84confirm the addition of the propargyl group. Cell viability assays using resazurin as an indicator

show the effectiveness of compounds n=13 or 15,R=propargyl or methyl, against Escheria coli (above)and methicillin-resistant Staphylococcus aureus (below).Concentrations begin at 125 g/mL for MRSA and1mg/mL for E. coli and decrease by 50% for eachdilution.

The IR spectra of N- octadecyl(cyanoethyl)amine, N- octadecyl(3-acetamidopropyl)amine, and N- octadecyl(3-acetamidopropyl) N-propargylammonium bromide [top to bottom respectively] provideconfirmation of each product as the nitrile stretch from the startingmaterial disappears while and amide stretch appears and finallythe alkyne stretch of the propargyl group appear in the finalproduct.

Antimicrobial analysis